This invention relates to a method for purifying and crystallizing benzphetamine acid salt by means of a convenient process for inducing crystallization of the salt from a liquid organic medium.
The production of benzphetamine has been known for a considerable period of time and was disclosed in U.S. Pat. No. 2,789,138 to Heinzelman et al. The chemical name of the physioacitve material, benzphetamine, is d-N-methyl-N-benzyl-beta-phenylisopropylamine. According to that patent benzyl chloride is reacted with methamphetamine in the presence of a base, typically sodium carbonate. The reaction is typically carried out in a non-reactive organic medium such as benzene, toluene, xylene or the like. The product is recovered by mixing the reaction mixture with water, extracting with medium, and then fractionally distilling at temperatures of about 127° C. and at a pressure of 0.2 mm of mercury, then converting the benzphetamine to the hydrochloride by addition of hydrochloric acid. The thus produced acid salt, typically in the form of an oil, is crystallized from the medium by the addition of ether. Such purification process has several disadvantages including the exposure of the product to high temperatures, and the need for expensive vacuum pumps and a vacuum still to achieve the desired reduced pressure.
In organic chemistry it is common to provide purification and isolation procedures that involve such standard operations as refluxing, azeotropic distillation, liquid partitioning and crystallization. Such processes are demonstrated by U.S. Pat. Nos. 6,489,343 and 6,458,830. While these patents are not concerned with the product of concern herein, they are representative of the above noted procedures for purification and isolation of product. In U.S. Pat. No. 5,236,922, the preparation and isolation of 1-(aminophenyl)-2-aminopropaneone derivatives are disclosed. The product 1-(4-acetylamino-3-chlorophenyl)-2-chrolopropanone was recrystallized from toluene. In U.S. Pat. No. 4,277,420 ephedrine and pseudoephedrine precursors described as N-(1-aroyl-1-alkenylamides were recrystallized from toluene. In U.S. Pat. No. 1,854,553 the production of ethyl benzylaniline by reacting monethylaniline with benzyl chloride is disclosed. The product is recovered from toluene by distillation.
Typically, benzphetamine hydrochloride forms an oil in the current processes that then require vacuum distillation to separate the oil from the reaction medium and provide a material that can be crystallized. While methods described in the above noted U.S. Pat. No. 2,789,138 are considered the standard whereby benzphetamine hydrochloride is currently manufactured, there is needed a convenient method for providing crystalline benzphetamine hydrochloride directly from the reaction medium rather than isolating it by distillation followed by crystallization. Further, it has been found that water/medium extraction leads to the need for further purification. Therefore, a process is needed that provides for isolation of the product in crystalline form in a manner that eliminates as much as possible any water from the system.